Anxiolytic-like effect of Suanzaoren–Wuweizi herb-pair and evidence for the involvement of the monoaminergic system in mice based on network pharmacology

Abstract

Background Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. Results The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. Conclusions The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Based on Network Pharmacology and Molecular Docking, the Active Components, Targets, and Mechanisms of Flemingia philippinensis in Improving Inflammation Were Excavated

“…The selected biological species was homo sapiens to obtain the PPI. The obtained PPI network data information was also analyzed with the help of Cytoscape 3.9.1, and topological methods were further used to filter out the core targets in the PPI network graphs based on degree centrality (DC), betweenness centrality (BC), and closeness centrality (CC) [ 22 ].…”

Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair

“…Herbal pairs, the basic constituent units of herbal formulas, have special clinical significance in Chinese-medicine and have gradually become a hotspot of modern research. [11] Compared with a single drug, herbal pairs can act synergistically to promote the treatment of various diseases. Modern research shows that Angelica sinensis has antitumour, liver protection, anti-inflammatory, hypoglycemic, immune regulation, cardiovascular and cerebral vascular system protection, etc, [12] and Radix Rehmanniae has the effect of regulating blood lipids and blood glucose, antiaging, antitumour, antibacterial, and protecting gastric mucosa, etc.…”